Incidence of dreaming during ciprofol anesthesia for painless gastroscopy.

BACKGROUND: Dreaming is often reported by patients who undergo propofol-based sedation, but there have not been any studies to date focused on the incidence of dreaming and factors associated therewith following the administration of ciprofol anesthesia in patients undergoing painless gastroscopy. The present study was thus developed with the goal of assessing the incidence of dreaming. METHODS: In total, this study enrolled 200 patients undergoing painless gastroscopy. During the procedure, patients' electroencephalographic Bispectral Index (BIS), blood pressure (BP), heart rate (HR), blood oxygen saturation (SpO2), and PETCO2 were monitored. When their MOAA/S score reached five after the procedure, patients were administered questionnaires including the Brice questionnaire and a five-point Likert Scale, and the content of any recalled dreams was also recorded. RESULTS: Overall, 27.5% of the participants in this study reported dreaming during the procedure, with most having experienced simple, pleasant dreams about everyday life. Identified predictors of dreaming during painless gastroscopy included lower ASA grade, preoperative knowledge of painless examination, a higher frequency of dreams in the month before the procedure, poor sleep quality during the month before the procedure, and shorter awakening time. Dreamers showed significantly lower BIS values at 2 min after endoscope insertion and following endoscope removal, and also showed lower minimum BIS values compared with non-dreamers. CONCLUSIONS: The postoperative dream recall incidence in this study was 27.5% among patients undergoing painless gastroscopy under ciprofol sedation anesthesia.

ß-adrenoceptor antagonists and nightmares: A pharmacoepidemiological-pharmacodynamic study.

AIM: To compare different ß-adrenoceptor antagonists for the risk of reporting nightmare. METHODS: The study involved two approaches: first, we investigated in VigiBase®, the World Health Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each ß-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological-pharmacodynamic analysis, we assessed whether use of ß-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT1A affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions. RESULTS: Of the 126,964 reports recorded with ß-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19-3.61), metoprolol (1.89, 1.66-2.16), and alprenolol (1.77, 1.06-2.97). Compared to use of low lipid solubility ß-adrenoceptor antagonists, use of moderate or high lipid solubility ß-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47-2.00 and aROR high vs. low 1.84, 95%CI 1.53-2.22). Use of moderate or high 5-HT1A affinity of ß-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT1A affinity of ß-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04-1.43 and aROR high vs. low 2.46, 95%CI 1.93-3.13). CONCLUSION: In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among ß-adrenoceptor antagonists with high lipid solubility and high 5-HT1A receptor affinity.

ß-Blockers and the Risk of New-Onset Depression: Meta-analysis Reassures, but the Jury Is Still Out.

ß-Blockers (BBs) are prescribed to a wide range of patients with cardiovascular and neuropsychiatric disorders. For more than half a century, BB treatment has been associated with depression as an adverse effect. The evidence in support of this association includes case reports, observational studies, and randomized controlled trials (RCTs). However, a large number of studies that refute the association have also been published. A very large meta-analysis of the psychiatric adverse effects of BBs, as reported in RCTs, was recently published. This meta-analysis found that BBs were not associated with an increased risk of depression or of withdrawal due to depression in comparison with either placebo or active controls. However, BBs were associated with an increased risk of fatigue/tiredness in comparison with placebo as well as in comparison with some groups of active controls. BBs were additionally associated with an increased risk of unusual dreams, relative to placebo. These findings suggest that fatigue/tiredness and unusual dreams may be misinterpreted by patients and clinicians as depression, explaining why BBs have been associated with depression risk. Furthermore, because BBs are commonly prescribed to patients with ischemic heart disease (IHD), and because IHD patients are at increased risk of depression, confounding by indication may explain why some patients treated with BBs later develop depression. These considerations notwithstanding, there are many reasons why the findings of the meta-analysis cannot be taken as reassurance on the subject. As examples, the RCTs in the meta-analysis mostly ascertained depression as a symptom rather than as a clinical diagnosis; and the meta-analysis did not consider risks with specific BBs such as propranolol, which has been strongly associated with the risk of depression in previous studies. In short, the final word, perhaps, remains to be said.

Doxazosin improved COVID-19 associated nightmare in a patient with major depressive disorder: a case report with a positive rechallenge.

This article reports on the treatment of a patient with nightmares who was treated with doxazosin of an alpha 1-adrenergic antagonists. A 71-year-old Japanese major depressive disorder (MDD) woman experienced nightmares after the coronavirus disease 2019 pandemic. She had nightmares about being chased by a coronavirus and catching the corona virus. After adding doxazosin 1 mg daily in the morning, her nightmares led to remission without side effects. We also had a rechallenge regimen with doxazosin. The nightmares ceased on the second night of the rechallenge and did not return with continued treatment. This case report suggests that doxazosin may be a useful therapeutic option to target nightmares in individuals with MDD.

[Rivastigmine as treatment for flashbacks and REM sleep problems in an older patient]. / Rivastigmine tegen herbelevingen en remslaapstoornissen bij een oudere patiënte.

A 61-year-old woman with suspected schizophrenia has been attending an outpatient geriatrics service for some time, initially with memory complaints and panic attacks. During treatment, the diagnosis schizophrenia was rejected and psychopharmaceuticals were largely phased out, which improved cognitive functions. Eventually, flashbacks of incest experienced in childhood remained together with REM sleep pathology. The flashbacks, nightmares and the REM sleep pathology were responsive to rivastigmine. Rivastigmine use for the treatment of REM sleep pathology is known in the literature, but it has never been described previously that rivastigmine also impacts on flashbacks and nightmares..

Comparative Effects of Dexmedetomidine and Midazolam on Dreaming of Patients Undergoing Flexible Bronchoscopy During General Anesthesia.

BACKGROUND The aim of this study was to compare the effects of dexmedetomidine versus midazolam on the dreaming of patients undergoing flexible bronchoscopy during general anesthesia. MATERIAL AND METHODS Patients undergoing flexible bronchoscopy under general anesthesia were randomly divided into a dexmedetomidine group (Group D, n=40) and a midazolam group (Group M, n=40). In group D, patients received 0.5 µg/kg dexmedetomidine and in group M patients received 0.05 mg/kg midazolam intravenously 10 min prior to induction. After bronchoscopy and recovery, a modified Brice questionnaire was used to immediately evaluate the incidence of dreaming of patients. Dreamers were required to complete a 5-point Likert scale survey regarding the contents of their dreams (emotion, voice and movement, memorability) if dreaming was reported. Ramsay Sedation Scale score (Ramsay score) and Visual Analogue Scale (VAS) score were assessed and recorded. RESULTS Patients in group D had higher Ramsay scores and VAS scores (2.9±0.6 and 79.4±4.0, respectively) than group M (2.4±0.7 and 75.0±6.0, respectively), with a statistically significant difference (P<0.05) between groups. The incidence and memorability of dreaming were significantly lower in group D (17.5%) than group M (37.5%, P<0.05), whereas no significant difference was found in emotion, voice, and movement scores of dreaming. CONCLUSIONS Compared to midazolam, pre-injection of dexmedetomidine before induction significantly decreased the incidence of dreaming in patients undergoing flexible bronchoscopy during general anesthesia, without producing undesirable effects on the content of dreams (most of them were pleasant), produces a more efficacious sedation effect during the recovery period and improves the comfort level and satisfaction of patients.

No cognitive processing in the unconscious, anesthetic-like, state of sleep.

We review evidence challenging the hypothesis that memories are processed or consolidated in sleep. We argue that the brain is in an unconscious state in sleep, akin to general anesthesia (GA), and hence is incapable of meaningful cognitive processing-the sole purview of waking consciousness. At minimum, the encoding of memories in sleep would require that waking events are faithfully transferred to and reproduced in sleep. Remarkably, however, this has never been demonstrated, as waking experiences are never truly replicated in sleep but rather appear in very altered or distorted forms. General anesthetics (GAs) exert their effects through endogenous sleep-wake control systems and accordingly GA and sleep share several common features: sensory blockade, immobility, amnesia and lack of awareness (unconsciousness). The loss of consciousness in non-REM (NREM) sleep or to GAs is characterized by: (a) delta oscillations throughout the cortex; (b) marked reductions in neural activity (from waking) over widespread regions of the cortex, most pronounced in frontal and parietal cortices; and (c) a significant disruption of the functional connectivity of thalamocortical and corticocortical networks, particularly those involved in "higher order" cognitive functions. Several (experimental) reports in animals and humans have shown that disrupting the activity of the cortex, particularly the orbitofrontal cortex, severely impairs higher order cognitive and executive functions. The profound and widespread deactivation of the cortex in the unconscious states of NREM sleep or GA would be expected to produce an equivalent, or undoubtedly a much greater, disruptive effect on mnemonic and cognitive functions. In conclusion, we contend that the unconscious, severely altered state of the brain in NREM sleep would negate any possibility of cognitive processing in NREM sleep.

Clinical Use of Prazosin in a Patient With Acute Stress Disorder: A Case Report.

Prazosin is an alpha-1 blocker that is commonly given to patients with posttraumatic stress disorder (PTSD) to reduce nightmares and flashbacks. Its use in acute stress disorder (ASD), however, has not been well characterized. There is a moderately positive correlation between ASD and the subsequent development of PTSD, which indicates that there may be some common neurobiological mechanisms that connect the 2 conditions. We present the case of a 51-year-old man who was experiencing symptoms of ASD following a motor vehicle accident that occurred a few days earlier. He was reporting flashbacks and nightmares of the accident, but after being treated with prazosin, his symptoms completely resolved. Prazosin may be effective in treating the symptoms of ASD and, by doing this, it may also play a role in inhibiting the progression of ASD to PTSD.

Nightmares and the Cannabinoids.

The cannabinoids, Δ9 tetrahydrocannabinol and its analogue, nabilone, have been found to reliably attenuate the intensity and frequency of post-traumatic nightmares. This essay examines how a traumatic event is captured in the mind, after just a single exposure, and repeatedly replicated during the nights that follow. The adaptive neurophysiological, endocrine and inflammatory changes that are triggered by the trauma and that alter personality and behavior are surveyed. These adaptive changes, once established, can be difficult to reverse. But cannabinoids, uniquely, have been shown to interfere with all of these post-traumatic somatic adaptations. While cannabinoids can suppress nightmares and other symptoms of post-traumatic stress disorder, they are not a cure. There may be no cure. The cannabinoids may best be employed, alone, but more likely in conjunction with other agents, in the immediate aftermath of a trauma to mitigate or even abort the metabolic changes which are set in motion by the trauma and which may permanently alter the reactivity of the nervous system. Steps in this direction have already been taken.

The effects of prazosin on sleep disturbances in post-traumatic stress disorder: a systematic review and meta-analysis.

BACKGROUND: Nightmares are a highly prevalent and distressing feature of post-traumatic stress disorder (PTSD). Previous studies have reached mixed conclusions regarding the effects of prazosin on nightmares, sleep quality, and overall PTSD symptoms in patients with PTSD. METHODS: MEDLINE, EMBASE, all EBM databases, PsycIFNO, and CINAHL were systematically searched from inception date to October 2018 for randomized clinical trials that included reporting of nightmares, sleep quality or overall PTSD symptoms. The analysis included data from eight trials involving 286 PTSD patients in the prazosin group and 289 PTSD patients in the placebo group. RESULTS: In our meta-analysis, prazosin resulted in a statistically significant improvement in nightmares (standardized mean difference (SMD) = -1.13, 95% confidence interval (CI) = -1.91 to -0.36), but was not more beneficial than placebo for overall PTSD symptoms (SMD = -0.45, 95% CI = -0.95 to 0.05) and sleep quality (SMD = -0.44, 95% CI = -1.44 to 0.55). In terms of acceptability, there was no significant difference between the prazosin group and the placebo group with respect to discontinuation for all causes (odds ratio (OR) = 1.00, 95% CI = 0.62-1.62). In conclusion, the use of prazosin was associated with an improvement of nightmare symptoms. CONCLUSION: Our findings indicate that additional studies are needed before considering downgrading the use of prazosin in the treatment of nightmares in patients with PTSD.

Comparative efficacy of imagery rehearsal therapy and prazosin in the treatment of trauma-related nightmares in adults: A meta-analysis of randomized controlled trials.

Pharmacological treatment with prazosin and psychological treatment with imagery rehearsal therapy (IRT) are the two main treatments of posttraumatic nightmares. The American Academy of Sleep Medicine task force recently listed IRT as the recommended treatment for trauma-related nightmares and changed the recommendation of prazosin to 'may be used'. This new recommendation was based on a single prazosin trial and not on a meta-analytic review of all available trials. The current meta-analysis aims to fill this gap in the literature. Eight studies on IRT and seven studies on prazosin (N = 1.078) were analyzed based on the random effects model. Relative to control groups, prazosin had a moderate to large effect on nightmare frequency (g = 0.61), posttraumatic stress symptoms (g = 0.81), and sleep quality (g = 0.85). IRT showed small to moderate effects on nightmare frequency (g = 0.51), posttraumatic symptoms (g = 0.31), and sleep quality (g = 0.51). No significant differences in effect were observed between prazosin and IRT on any of these outcomes (all p's > 0.10). It is concluded that downgrading the recommendation of prazosin may be a premature decision and that the aggregated results in this meta-analysis clearly show efficacy of both treatments.

Nightmares and hallucinations with aprepitant and opium powder: a suspected drug-drug interaction.

Polypharmacy of elderly oncology patients and fragmented medication management are well-known risk factors for drug-drug interactions (DDIs). These interactions can occur among antineoplastic, ongoing chronic treatment(s) and chemotherapy-associated treatments, like antiemetics. Clinically relevant interactions based on enzyme- or transporter-inhibition phenomena of active drugs can increase the frequency of their DDIs. We describe a strongly suspected elderly cancer patient's DDI between aprepitant and opium powder in the context of an irinotecan-based regimen manifested by nightmares and visual hallucinations. We discuss this DDI's hypothetical pharmacological mechanisms and management.

Management of Post-Traumatic Nightmares: a Review of Pharmacologic and Nonpharmacologic Treatments Since 2013.

PURPOSE OF REVIEW: Post-traumatic nightmares (PTN) are a common and enduring problem for individuals with post-traumatic stress disorder (PTSD) and other clinical presentations. PTN cause significant distress, are associated with large costs, and are an independent risk factor for suicide. Pharmacological and non-pharmacological treatment options for PTN exist. A previous review in this journal demonstrated that Prazosin, an alpha blocker, was a preferred pharmacological treatment for PTN and imagery rescripting therapy (IRT) was a preferred non-pharmacological treatment. Since that time, new and important research findings create the need for an updated review. RECENT FINDINGS: Based on the results of a recent study in the New England Journal of Medicine, Prazosin has been downgraded by both the American Academy of Sleep Medicine (AASM) and the Veterans Health Administration/Department of Defense (VA/DoD) for PTN. In Canada, Nabilone, a synthetic cannabinoid, appears to be promising. Few recent studies have been published on non-pharmacological interventions for PTN; however, recent data is available with regard to using IRT on an inpatient setting, with German combat veterans, and through the use of virtual technology. Recent evidence supports the use of exposure, relaxation, and rescripting therapy (ERRT) with children and individuals with comorbid bipolar disorder and PTN. Prazosin is no longer considered a first-line pharmacological intervention for PTN by AASM and VA/DoD. However, in the absence of a suitable alternative, it will likely remain the preferred option of prescribers. IRT and ERRT remain preferred non-pharmacological treatments of PTN. Combining cognitive behavior therapy for insomnia (CBT-I) with IRT or ERRT may lead to improved outcomes.

A Pilot, Randomized Clinical Trial of Bedtime Doses of Prazosin Versus Placebo in Suicidal Posttraumatic Stress Disorder Patients With Nightmares.

PURPOSE/BACKGROUND: Observational studies show an association between nightmares and suicide. Prazosin is proposed as a nightmare treatment. This pilot, randomized clinical trial tested whether treatment of nightmares with prazosin would reduce suicidal ideas in suicidal posttraumatic stress disorder (PTSD) patients. METHODS/PROCEDURES: Twenty adult, suicidal PTSD patients with nightmares were blindly and randomly assigned 1:1 to escalating doses of prazosin versus placebo at bedtime only for 8 weeks. All participants had comorbid mood disorders and received stable doses of mood disorder medication. Outcomes of interest were measured weekly and included severity of suicidal ideation, nightmares, PTSD, insomnia, and depression. Longitudinal mixed-effects models assessed change in outcomes over time. FINDINGS/RESULTS: All psychometric measures improved over 8 weeks. However, nighttime measures of nightmares and insomnia showed significantly less improvement in the prazosin group, whereas there was no significant change in daytime measures of suicidal ideation and daytime-only PTSD symptoms. Two patients required emergency psychiatric hospitalization, but there were no suicide attempts and no deaths. IMPLICATIONS/CONCLUSIONS: This study confirmed an effect of nighttime-only prazosin on nighttime symptoms of insomnia and nightmares in suicidal PTSD patients who are experiencing nightmares. Surprisingly, the effect was in the direction opposite of what we expected. Furthermore, prazosin showed no signal on daytime measures including suicidal ideation. The results do not support a larger study of nighttime-only prazosin in suicidal PTSD patients but leave open the possibility of benefit from daytime administration of prazosin.

Pre-sleep treatment with galantamine stimulates lucid dreaming: A double-blind, placebo-controlled, crossover study.

Lucid dreaming is a remarkable state of consciousness in which one is aware of the fact that one is dreaming while continuing to dream. Based on the strong relationship between physiological activation during rapid eye-movement sleep and lucid dreaming, our pilot research investigated whether enhancing cortical activation via acetylcholinesterease inhibition (AChEI) would increase the frequency of lucid dreams and found AChEI to be a promising method for lucid dream induction. In the current study we sought to quantify the size and reliability of the effect of AChEI on lucid dreaming, dream recall and dream content as well as to test the effectiveness of an integrated lucid dream induction protocol which combined cholinergic stimulation with other methods for lucid dream induction. Participants (N = 121) with high dream recall and an interest in lucid dreaming were randomly assigned counterbalanced orders of 3 doses of galantamine (0, 4 and 8 mg). On 3 consecutive nights, they awoke approximately 4.5 hours after lights out, recalled a dream, ingested the capsules and stayed out of bed for at least 30 minutes. Participants then returned to bed and practiced the Mnemonic Induction of Lucid Dreams technique while returning to sleep. The percentage of participants who reported a lucid dream was significantly increased for both 4 mg (27%, odds ratio = 2.29) and 8 mg doses (42%, odds ratio = 4.46) compared to the active placebo procedure (14%). Galantamine also significantly increased dream recall, sensory vividness and complexity (p<0.05). Dream recall, cognitive clarity, control, positive emotion, vividness and self-reflection were increased during lucid compared to non-lucid dreams (p<0.0001). These results show that galantamine increases the frequency of lucid dreams in a dose-related manner. Furthermore, the integrated method of taking galantamine in the last third of the night with at least 30 minutes of sleep interruption and with an appropriately focused mental set is one of the most effective methods for inducing lucid dreams available today.

Exploring the effects of galantamine paired with meditation and dream reliving on recalled dreams: Toward an integrated protocol for lucid dream induction and nightmare resolution.

An experimental home study examined the impact of a pre-sleep protocol for enhancing self-awareness, lucidity, and responsiveness in dreams. It included ingesting the cholinesterase inhibitor galantamine--which is widely reported to increase the frequency of lucid dreaming--prior to engaging in middle-of-the-night meditation and the imaginary reliving of a distressing dream while exercising new responses. Thirty-five participants completed an eight-night study, which included pre- and post-baseline nights and six conditions: waking for 40 min before returning to bed, called Wake-Back-to-Bed (WBTB); Wake-Back-to-Bed plus placebo (WBTB + P); Wake-Back-to-Bed plus galantamine (WBTB + G); meditation and dream reliving (MDR); meditation and dream reliving plus placebo (MDR + P); and meditation and dream reliving plus galantamine (MDR + G). The outcome measures included lucidity, reflectiveness, interactive behavior, role change, constructive action, and fear and threat, as measured by the participants' self-ratings. The results support the use of this protocol in further studies of lucid dream induction and nightmare/trauma resolution.

Dreaming and awareness during dexmedetomidine- and propofol-induced unresponsiveness.

BACKGROUND: Experiences during anaesthetic-induced unresponsiveness have previously been investigated by interviews after recovery. To explore whether experiences occur during drug administration, we interviewed participants during target-controlled infusion (TCI) of dexmedetomidine or propofol and after recovery. METHODS: Healthy participants received dexmedetomidine (n=23) or propofol (n=24) in stepwise increments until loss of responsiveness (LOR1). During TCI we attempted to arouse them for interview (return of responsiveness, ROR1). After the interview, if unresponsiveness ensued with the same dose (LOR2), the procedure was repeated (ROR2). Finally, the concentration was increased 1.5-fold to achieve presumable loss of consciousness (LOC), infusion terminated, and the participants interviewed upon recovery (ROR3). An emotional sound stimulus was presented during LORs and LOC, and memory for stimuli was assessed with recognition task after recovery. Interview transcripts were content analysed. RESULTS: Of participants receiving dexmedetomidine, 18/23 were arousable from LOR1 and LOR2. Of participants receiving propofol, 10/24 were arousable from LOR1 and two of four were arousable from LOR2. Of 93 interviews performed, 84% included experiences from periods of unresponsiveness (dexmedetomidine 90%, propofol 74%). Internally generated experiences (dreaming) were present in 86% of reports from unresponsive periods, while externally generated experiences (awareness) were rare and linked to brief arousals. No within drug differences in the prevalence or content of experiences during infusion vs after recovery were observed, but participants receiving dexmedetomidine reported dreaming and awareness more often. Participants receiving dexmedetomidine recognised the emotional sounds better than participants receiving propofol (42% vs 15%), but none reported references to sounds spontaneously. CONCLUSION: Anaesthetic-induced unresponsiveness does not induce unconsciousness or necessarily even disconnectedness. CLINICAL TRIAL REGISTRATION: NCT01889004.

Effects of Vitamin B6 (Pyridoxine) and a B Complex Preparation on Dreaming and Sleep.

Anecdotal evidence indicates that supplementation with vitamin B6 (pyridoxine) before bed can enhance dream vividness and recall. In a single pilot study, Ebben, Lequerica, and Spielman (2002) found that vitamin B6 had a dose-dependent effect of increasing scores on a composite measure of dream vividness, bizarreness, emotionality, and color. The present research replicated this study using a larger and more diverse sample of 100 participants from across Australia. We conducted a randomized, double-blind, placebo-controlled investigation of the effects on dreaming and sleep of ingesting 240 mg vitamin B6 (pyridoxine hydrochloride) before bed for five consecutive days. We also included an exploratory condition involving a B complex preparation containing a range of B vitamins. We found that vitamin B6 significantly increased the amount of dream content participants recalled but did not significantly affect dream vividness, bizarreness, or color, nor did it significantly affect other sleep-related variables. In contrast, participants in the B complex group showed significantly lower self-rated sleep quality and significantly higher tiredness on waking. We discuss the potential for using vitamin B6 in research on lucid dreaming.